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Antimicrob. Agents Chemother. doi:10.1128/AAC.01130-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

High levels of AZT and its intracellular phosphate metabolites in AZT and AZT/3TC-treated newborns of HIV-infected mothers

CEA, iBiTecS, Service de Pharmacologie et d'Immunoanalyse, Gif sur Yvette, F-91191, France; AP-HP, Hôpital Armand Trousseau, Service de virologie, Paris, F-75012 France; Université Pierre et Marie Curie-Paris 6, EA 3500, Paris, F-75012 France; AP-HP, Hôpital Armand Trousseau, Service d'hématologie et d'oncologie pédiatrique, Paris, F-75012 France; CEA, Direction des Sciences du Vivant, CEA/Saclay, 91191 Gif-sur-Yvette Cedex, France

^* To whom correspondence should be addressed. Email: henri.benech{at}cea.fr.

	Abstract

Newborns from HIV-infected mothers are given antiretroviral prophylaxis against mother-to-child transmission, including predominantly nucleoside reverse transcriptase inhibitors. Pharmacological monitoring of these drugs in newborns has been so far limited to plasma and cord blood. In this study, samples from newborns (up to 45 days) treated by zidovudine (AZT) alone (n = 29) or in combination with lamivudine (3TC, n = 20) were analyzed for both intracellular concentrations of phosphate metabolites in peripheral blood mononuclear cells (PBMC) and levels of parent drugs in plasma.

Plasma AZT and intracellular AZT-MP and AZT-TP concentrations were significantly high during the first fifteen days of life (199 versus 52.7 ng/mL P<0.0001, 732 versus 282 fmol/10⁶ cells P<0.0001, and 170 versus 65.1 fmol/10⁶ cells P<0.0001, respectively) and then became comparable to adults. No difference in intracellular AZT metabolites concentrations was found when comparing AZT and AZT/3TC-treated groups.

Plasma 3TC levels (LLOQ-1157 ng/mL, median 412.5 ng/mL) were not associated with the newborn's age, gender, or weight. Intracellular 3TC-TP concentrations (LLOQ-40.4 pmol/10⁶ cells, median 18.9 pmol/10⁶ cells) determined in newborns receiving the AZT/3TC combination were associated with neither the age nor weight of the newborns. Concentrations in females were significantly higher (1.8-fold; P = 0.0415) than those in males. Unexpectedly newborns on AZT monotherapy, whose mother's treatment included 3TC, displayed residual plasma 3TC and intracellular 3TC-TP up to one week after birth.